The Applicant company has chosen to develop its invention in a field which is known for the dangerousness of the contaminants that may be introduced via glucose polymers, said contaminants being responsible for inflammatory reactions that are very harmful to human health: the field of peritoneal dialysis.
Peritoneal dialysis is a type of dialysis of which the objective is to remove waste such as urea, creatinine, excess potassium or surplus water that the kidneys do not manage or no longer manage to purify out of the blood plasma. This medical treatment is indicated in the event of end-stage chronic renal failure.
It is an intracorporeal purification which uses the peritoneum as a dialysis membrane. Toxic waste from the blood crosses the semi-permeable membrane of the peritoneum, to a solution known as a dialysate. The dialysate is introduced into the peritoneal cavity via a permanent catheter. There are two types of peritoneal dialysis:                CAPD (continuous ambulatory peritoneal dialysis), a treatment which is based on passing through four bags of dialysate per day according to medical prescription,        APD (automated peritoneal dialysis), a continuous nocturnal treatment which corresponds to approximately 15 liters of dialysate per 8 hours according to medical prescription.        
The dialysates most commonly used are composed of a buffer solution (of lactate or of bicarbonate) at acid pH (5.2-5.5) or physiological pH (7.4), to which electrolytes (sodium, calcium, magnesium, chlorine) and an osmotic acid (glucose or a glucose polymer, such as “icodextrin” present in the Extraneal® ambulatory peritoneal dialysis solution sold by the company Baxter) are added.
The glucose polymer, such as icodextrin mentioned above, is preferred to glucose as osmotic agent because, owing to its small size, the glucose which rapidly crosses the peritoneum leads to a loss of osmotic gradient in the 2 to 4 hours of infusion.
The standard glucose polymers are produced by acid or enzymatic hydrolysis of starch from cereals or from tuberous plants.
Acid hydrolysis of starch, which is completely random, or enzymatic hydrolysis thereof, which is slightly more ordered, provides mixtures of glucose (monomer) and glucose chains which comprise very short molecules (oligomers), with a low degree of polymerization (or DP), and very long molecules (polymers), with a high DP. Glucose polymers have, moreover, an extremely varied molecular weight.
In the more particular field of the use of glucose polymers for continuous ambulatory peritoneal dialysis, it very quickly became apparent that these starch hydrolysates (mixture of glucose, and of glucose oligomers and polymers) could not be used as such.
European patent application EP 207 676 teaches that glucose polymers forming clear and colorless solutions at 10% in water, having a weight-average molecular weight (Mw) of 5 000 to 100 000 daltons and a number-average molecular weight (Mn) of less than 8 000 daltons are preferred.
Such glucose polymers also preferably comprise at least 80% of glucose polymers of which the molecular weight is between 5 000 and 50 000 daltons, little or no glucose or glucose polymers with a DP less than or equal to 3 (molecular weight 504) and little or no glucose polymers with a molecular weight greater than 100 000 (DP of about 600).
In other words, the preferred glucose polymers are glucose polymers with a low polydispersity index (value obtained by calculating the Mw/Mn ratio).
The methods proposed in that patent application EP 207 676 for obtaining these glucose polymers with a low polydispersity index from starch hydrolysates consist:                either in carrying out a fractional precipitation of a maltodextrin with a water-miscible solvent,        or in carrying out a molecular filtration of this same maltodextrin through various membranes possessing an appropriate cut-off or exclusion threshold.        
In the two cases, these methods are aimed at removing at the same time the very high-molecular-weight polymers and the low-molecular-weight monomers or oligomers.
However, these methods do not provide satisfaction both from the point of view of their implementation and from the point of view of the yields and the quality of the products that they make it possible to obtain.
In the interests of developing a method for producing a completely water-soluble glucose polymer with a low polydispersity index preferentially less than 2.5, preferably having an Mn of less than 8 000 daltons and having an Mw of between 12 000 and 20 000 daltons, said method lacking the drawbacks of the prior art, the Applicant company endeavored to solve this problem in its patent EP 667 356, by starting from a hydrolyzed starch rather than from a maltodextrin.
The glucose polymer obtained by chromatographic fractionation then preferably contains less than 3% of glucose and of glucose polymers having a DP less than or equal to 3 and less than 0.5% of glucose polymers having a DP greater than 600.
It is finally henceforth accepted by experts in the field of peritoneal dialysis that these glucose polymers, used for their osmotic power, are entirely satisfactory.
However, risks of microbial contamination of these preparations intended for peritoneal dialysis are to be deplored.
It is in fact known that glucose polymer production circuits can be contaminated with microorganisms, or with pro-inflammatory substances contained in said microorganisms.
The contamination of corn or wheat starches with microorganisms of yeast, mold and bacteria type, and more particularly with acidothermophilic bacteria of Alicyclobacillus acidocaldarius type (extremophilic bacteria which grow in the hot and acidic zones of the circuit) is, for example, described in the starch industry.
The major risk for the patient who receives these contaminated products is then peritonitis.
Clinical suspicion of peritonitis is diagnosed when there is a cloudy dialysate together with variable clinical manifestations, namely abdominal pain, nausea, vomiting, diarrhea and fever.
These episodes of peritonitis are caused by intraperitoneal bacterial infections, and the diagnosis usually easily established through positive dialysate cultures.
“Sterile peritonitis”, which is also described as aseptic, chemical or culture-negative peritonitis, is, for its part, typically caused by a chemical irritant or a foreign body.
Since the introduction of icodextrin for the preparation of peritoneal dialysis solutions, isolated cases of aseptic peritonitis have been reported, that can be linked to various causes, and in particular induction by pro-inflammatory substances potentially present.
Aseptic inflammatory episodes are therefore major complications observed after injections of dialysis solutions.
While some of these inflammatory episodes are linked to a problem of chemical nature (accidental injection of chemical contaminants or incorrect doses of certain compounds), the majority of cases are directly associated with the presence of contaminants of microbial origin that are present in the solutions used to prepare the dialysis solutions.
Lipopolysaccharides (LPSs) and peptidoglycans (PGNs) are the main contaminants of microbial origin which present a high risk of triggering an inflammation when they are present in trace amounts.
The standard tests theoretically make it possible to discard batches which are loaded with contaminants of this type and which therefore present a health risk. However, these tests are not satisfactory, since aseptic inflammatory episodes are still reported, even though the solutions had been declared healthy.
Thus, despite the constant attention of those participating the field, in terms of reducing the risk of contaminations, in particular by improving detection thereof, there still remains a need to improve the performance levels of the detection of contaminants which can induce an inflammation.